Amyloid-beta induces distinct forms of cell death in different neuronal populations.

Recent FDA approval for treating Alzheimer's disease (AD) with amyloid-beta (Aβ) immunotherapy is a historic breakthrough, which has rekindled widespread interest in understanding the molecular basis of Aβ toxicity. In this study, we developed a novel Drosophila model to investigate Aβ42-induced pathologies in vivo and in real time. Strikingly, we unveiled compelling evidence that secreted Aβ42 affects different neurons in distinct ways-both in susceptibility to Aβ42 deposition and in the mode of cell death triggered. Additionally, we observed altered larval crawling behaviour which-remarkably-could be recovered by inhibiting ferroptotic cell death with small molecule inhibitors. Collectively these findings showcase this as a powerful new model for investigating Aβ toxicity in AD and identifying novel treatment strategies.